title: Persistent epigenetic differences associated with prenatal exposure to famine in humans.
abstract: Extensive epidemiologic studies have suggested that adult disease risk is associated with adverse environmental conditions early in development. Although the mechanisms behind these relationships are unclear, an involvement of epigenetic dysregulation has been hypothesized. Here we show that individuals who were prenatally exposed to famine during the Dutch Hunger Winter in 1944-45 had, 6 decades later, less DNA methylation of the imprinted IGF2 gene compared with their unexposed, same-sex siblings. The association was specific for periconceptional exposure, reinforcing that very early mammalian development is a crucial period for establishing and maintaining epigenetic marks. These data are the first to contribute empirical support for the hypothesis that early-life environmental conditions can cause epigenetic changes in humans that persist throughout life.
authors.affiliation: Departments of Molecular Epidemiology, Medical Statistics, and Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands. b.t.heijmans@lumc.nl
authors.forename: Bastiaan T
authors.initials: BT
authors.lastname: Heijmans
authors.forename: Elmar W
authors.initials: EW
authors.lastname: Tobi
authors.forename: Aryeh D
authors.initials: AD
authors.lastname: Stein
authors.forename: Hein
authors.initials: H
authors.lastname: Putter
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Blauw
authors.forename: Ezra S
authors.initials: ES
authors.lastname: Susser
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.forename: L H
authors.initials: LH
authors.lastname: Lumey
mesh_terms: D000328:Adult; D001724:Birth Weight; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D039401:Prenatal Nutritional Physiological Phenomena / Q000235:genetics*; D013217:Starvation / Q000453:epidemiology / Q000235:genetics*
chemical_list: C035170:IGF2 protein, human; D007335:Insulin-Like Growth Factor II